Choosing Wisely: Cardiovascular Drug Therapy in the Era of COVID-19.

Abstract

In the light of physicians worldwide facing COVID-19, established therapy is challenged. Several observational studies have clearly shown that cardiovascular risk factors and comorbidities such as arterial hypertension or diabetes are more common in patients with a severe clinical course of COVID-19 than in those with mild or asymptomatic courses.1 Although at first sight this might be well explained as simple coincidence in elderly patients, other explanations need to be carefully considered. In this context, theoretical considerations based on findings from animal studies just recently triggered speculations regarding potential harmful effects of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers in patients with COVID-19 due to upregulation of membrane-bound ACE2. Conversely, large-scale population studies investigating this potential interaction did not show a direct negative effect of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers in neither risk of infection nor severity of COVID-19.2,3 Ongoing controversial discussions reveal that there are substantial gaps in knowledge regarding comorbidities and drug interactions in infectious diseases, in general, and COVID-19 specifically. In this issue of JCVP, Russo and colleagues highlight the prevalence of arrhythmias in COVID-19 patients and related mechanisms of COVID-19 infection induced arrhythmias.4 Pharmacological interactions between cardiovascular drugs commonly used in atrial fibrillation (AF) management and experimental COVID-19 therapy are listed and discussed. From the clinician's perspective, 2 issues related to the treatment of AF patients infected with COVID-19 nicely highlight potentially relevant pharmacological interactions, and therefore, from a mechanistical perspective are specifically worth further consideration: Cardiovascular Drugs Intervening With ACE2 Enzyme: 2 Sides of the Same Coin? Most AF patients either have a history of hypertension or suffer from chronic myocardial injury such as in ischemic or hereditary cardiomyopathy. Therefore, these patients regularly receive angiotensin-converting enzyme inhibitors or angiotensin receptor blockers. As stated above, increased membrane-bound ACE2 activity post angiotensin converting enzyme inhibitors/angiotensin receptor blockers (angiotensin converting enzyme inhibitors/angiotensin receptor blockers) on the one hand might promote the susceptibility and severity of severe acute respiratory syndrome (SARS)‐CoV‐2 infection, which is unfavorable for COVID-19 patients. However, vice versa, increased circulating soluble form of ACE2 might also act as a favorable factor, serving as a decoy receptor that binds to SARS-CoV-2, thus neutralizing the SARS-CoV-2 virus in the peripheral circulation.5 As a result, recommendations of the major professional scientific societies which uniformly remained unchanged regarding application of angiotensin converting enzyme inhibitorsangiotensin receptor blockers for cardiovascular patients infected with COVID-19 might turn out wisely not only from clinical experience but also the scientific viewpoint.5 Anticoagulation: 2 Birds With one Stone? Increasing evidence from cohort studies and autopsies suggests a substantial role of coagulopathy in the pathogenesis of COVID-19.6 Anticoagulation, on the other hand, was significantly related with lower mortality in COVID-19 patients with a treatment indication as compared with patients without anticoagulation during hospitalization for COVID-19.7,8 Here again, current recommendations suggest that in general established anticoagulation medication principles should remain unchanged for COVID-19 patients with or without AF. Future epidemical studies, however, might supply further evidence whether COVID-19 patients with an indication for anticoagulation—such as those with AF—might indeed have a better outcome as compared with COVID-19 patients without AF as a consequence of more frequent application of anticoagulation in AF patients. Today, comorbidities are well established as a key figure in the management of patients not only with cardiovascular but to an increasing extent also other diseases. The importance of comedication in the management of increasingly complex patients and diseases should not be underestimated and is most definitely worth further work of basic as well as clinical scientists. Here again, concluding an assessment exceeding current evidence from observational trials will definitely require randomized trial designs to allow judgment weighing up potential positive, as well as negative, pharmacological effects in clinical reality of COVID-19 but also many other diseases.